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Stone analysis Stone analysis Mostafa Sabry Abdullah Demonstrator Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University  Definition: Stone formation is a genetic, nutritional or environmental disease  Incidence: Recent studies indicate that over 10% of adult males suffering from urinary stone at least one  Mechanism of stone formation:  Urinary stones are always formed of substances that normally excreted in the urine  These substances for unknown causes are supersaturated to pass their solubility products leading to their precipitation and formation of crystals that bind together to form stones   Alternative names include:  Renal Lithiasis  Renal Calculi  Nephrolithiasis (Kidney Stone Disease) Depending on its location in the urinary tract it is called :  Kidney Stone  Ureteric Stone  Bladder Stone  Urethral Stone Classification of stones: Stones may be classified according to two methods:  A According to number of components: a) Simple stones: contain only single constituent e.g Ca oxalate b) Mixed stones: contain two or more constituent e.g Ca oxalate+ Ca& Mg phosphate  B According to type of components: 1) Ca Oxalate stones: (the most common in Egypt) 2) Ca Phosphate stones 3) Ca Carbonate stones 4) Mg Ammonium Phosphate stones 5) Uric acid stones: 4-10 % 6) Cystine stones: < 1% 7) Xanthin stones: very rare 8) Struvite Stones 9) Foreign body stones: formed of foreign body that introduced into the body from outside Kidney Stone Occurrence in When they form type Population Calcium oxalate 80 % when urine is acidic or alkaline Calcium 0% when urine is alkaline (high pH) Uric acid 5-10 % when urine is persistently acidic Struvite 10-15 % infections in the kidney Cystine 0% rare genetic disorder phosphate Calcium stones Struvite Stones Uric Acid stones Cystine Stones Factors affecting stone formation:1- Change urine pH:  Bacteria  Urea  NH3   pH   stone 2- Vitamins disturbances: e.g  - Exss Vit D   Ca absorption   Ca stones  - Exss Vit C   oxalate stones  -  Vit A Roughness of epithelial cells lining to the urinary tract  ppt of crystals crystal formation 3- Hormonal disturbance : e.g Hyperparathyroidism   Ca2+ stones 4-  uric acid level   uric acid stones 5-  mucoprotein: which act as a cement material to bind crystals   stones Risk factors for stone formation Renal risk factor  1- Infections,  2- Obstructions,  3- Parasitic infections, as:- schistosomiasis  4- Congenital anomalies Pre-urinary risk factors:  A) Intrinsic:  1-Hereditary:  2- Age:  3- Sex:  Mechanical factors : A) Intrinsic: 1-Hereditary:  Renal tubular acidosis :;  Primary hyperoxaluria;  Cystinuria;  Hyperuricosuria;  Absorptive hypercalciuria: this is the most common  Cushing syndrome  4- Occupation: There is a higher incidence of stone in sedentary workers (in the armed force, office personal have a higher risk than active units such as the royal marine)  5- Water: a) Amount: chronic dehydration stone disease b) Hot climate c) Hot occupation d) Low fluid intake: patients whose 24h urinary volumes are less than 1400 ml show an increased recurrence rate e) Composition: stone formation is higher in soft water areas than in hard water areas  6- Infection stones: Chronic infections in the urinary tract can cause renal calculi that are   Struvite: magnesium ammonium phosphate (Mg NH4.6H2O;) and Carbonate appetite: (Ca10PO4.6CO3) The most common found in stone patients are Proteus and Pseudomonas Inhibitors of stone formation:  a) Ions: citrate, magnesium, and pyrophosphate  b) Larger molecules:  Glycosaminoglycans (GAGs):  Nephrocalcin:  Complexers:  Glycosaminoglycans (GAGs):  They are polysaccharides chains of repeating disaccharides derived by degradation of high molecular weight proteoglycans;  GAG excretion is greater in male subjects, rising post- prandially and at night ; excretion rises by 50% in summer;  GAGs inhibit calcium oxalate crystallization  Nephrocalcin: It is a recently isolated γ- carboxy-glutamic acid-containing protein ; it inhibits calcium oxalate crystallization and may be structurally abnormal or deficient in some stone patients  Complexers: Specific charged ions combine with potential crystalline components to form soluble complexes reducing the free ionic concentration:  Anions such as citrate , phosphate , and sulphate complex calcium  Cations such as magnesium complex oxalate Promoters of stone formation:  Tamm- Horsfall protein and the organic matrix  The composition of the urine diurnal variation  The times associated with the highest supersaturation occur between and 10 a.m and between and 10 p.m  Meals cause variations, especially in the concentration of calcium  The highest excretion of oxalate and urate occurs early in the morning Tamm- Horsfall protein  It is the matrix of urinary casts derived from the secretion of renal tubular cells  When this protein is concentrated at low pH, it forms a gel  act as a constitutive inhibitor of calcium crystallization in renal fluids,provide defense against urinary tract infections Inhibitors Citrate Magnesium Pyrophosphate Glycosaminogly can • Nephrocalcin • High urine volume • • • • Promoters Calcium Sodium Oxalate Urate Low urine pH Tamm- Horsfall protein Low urine volume • • • • • • •

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